Predictive efficacy of combined tumor markers and gastrin for recurrence after endoscopic submucosal dissection in early gastric cancer patients.

OBJECTIVE: This study aims to evaluate the predictive value of tumor markers combined with gastrin for tumor recurrence after endoscopic submucosal dissection (ESD) in patients with early gastric cancer. METHODS: The clinicopathological data of 169 patients with early gastric cancer treated with ESD between March 2019 and January 2021 were retrospectively analyzed. The patients were divided into a relapse group (n=45) and a non-recurrence group (n=124). Clinical data such as carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), gastrin 17, pepsinogen I and pepsinogen II, as well as tumor size and degree of infiltration were examined to construct a recurrence prediction model using lasso regression. RESULTS: The comprehensive model showed superior predictive power (AUC=0.958, C-index=0.966) over biomarker-only models (AUC=0.925), indicating a significant improvement in the prediction of recurrence risk. Decision curve analysis confirmed the clinical utility of the model with a maximum net benefit of 73.37%. Key indicators such as CEA, CA19-9, AFP, gastrin 17 and pepsinogens I and II were statistically significant in predicting recurrence with P values < 0.01. CONCLUSION: The comprehensive model combining tumor markers with clinical data provides a more accurate and clinically valuable tool for predicting recurrence in early gastric cancer patients after ESD. This approach facilitates personalized risk assessment and may significantly improve prognostic management, emphasizing the importance of a multifaceted strategy in the management of early gastric cancer.

Synthesis and Evaluation of Novel 68Ga-Labeled [D-Phe6,Leu13ψThz14]bombesin(6-14) Analogs for Cancer Imaging with Positron Emission Tomography.

Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [68Ga]Ga-TacsBOMB2 ([68Ga]Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13ψThz14-NH2), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle10-derived Ga-LW01158, NMe-His12-derived Ga-LW01160, α-Me-Trp8- and Tle10-derived Ga-LW01186, and Tle10- and N-Me-Gly11-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (Ki(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [68Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 (76.5-80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle10 substitution, either alone or combined with α-Me-Trp8 or NMe-Gly11 substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [68Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.

Choledochoduodenostomy combined with Billroth II procedure for extrahepatic biliary obstruction and duodenal perforation in a cat.

Case summary: A 5-year-old neutered Somali cat presented with a 2-week history of icterus. Diagnostic imaging revealed extrahepatic biliary obstruction (EHBO) due to a common bile duct (CBD) mass. During exploratory laparotomy, a duodenal perforation was discovered incidentally. Choledochoduodenostomy combined with the Billroth II procedure was performed after resection of the CBD mass and the proximal duodenum to treat the EHBO and duodenal perforation. Based on histological and immunohistochemical findings, the CBD mass was diagnosed as a neuroendocrine carcinoma with gastrin-producing cell differentiation. The cat recovered almost uneventfully and was discharged 11 days after surgery. The cat survived for nearly 100 days without recurrence of EHBO or duodenal perforation; however, intermittent vomiting and weight loss persisted despite supportive medications. Relevance and novel information: To the best of our knowledge, there is no detailed report on the application of choledochoduodenostomy combined with the Billroth II procedure in cats, as we used to treat the EHBO and duodenal perforation in the present case. As serum gastrin concentrations were elevated on the first day of hospitalisation, the CBD mass was diagnosed as a neuroendocrine carcinoma with gastrin-producing cell differentiation, which seemed to have caused not only EHBO but also duodenal perforation (Zollinger-Ellison syndrome). The cat survived for almost 100 days without any perioperative complications. However, this combined procedure might be considered as only a salvage option and not as a definitive treatment option in cats requiring simultaneous biliary and gastrointestinal reconstruction because postoperative supportive care could not improve the cat's condition or maintain its quality of life.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.

Gastrin: a new branch of the gastropancreatic axis that can explain the effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Among bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide. METHODS: In 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured. RESULTS: SG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group. CONCLUSION: Gastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers.

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target.

Prospective Randomized Controlled Clinical Trial of the Long-Term Effects of Omeprazole on Healthy Dogs.

The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T0), 30 days after the start of treatment (T1), and at 60 days (T2). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T0, 481.4 (±170.21) at T1, and 513.2 (±174.50) at T2. In the omeprazole group, the values were 424.62 (±161.57) at T0, 454.5 (±160.96) at T1, and 414.87 (±127.90) at T2. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T0, 76.06 [30.67-199.87] at T1, and 63.02 [35.81-176.06] at T2. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T0, 191.77 [75.31-1901.77] at T1, and 128.16 [43.62-1066.46] at T2. Statistically significant differences were detected (p = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.

Evaluation of Gastric pH and Gastrin Concentrations in Horses Subjected to General Inhalation Anesthesia in Dorsal Recumbency.

The prevalence of gastric disorders in high-performance horses, especially gastric ulceration, ranges from 50 to 90%. These pathological conditions have negative impacts on athletic performance and health. This study was designed to evaluate changes in gastric pH during a 24 h period and to compare gastrin concentrations at different time points in horses undergoing general inhalation anesthesia and dorsal recumbency. Twenty-two mixed-breed mares weighing 400 ± 50 kg and aged 8 ± 2 years were used. Of these, eight were fasted for 8 h and submitted to 90 min of general inhalation anesthesia in dorsal recumbency. Gastric juice samples were collected prior to anesthesia (T0), and then at 15 min intervals during anesthesia (T15-T90). After recovery from anesthesia (45 ± 1 min), samples were collected every hour for 24 h (T1 to T24) for gastric juice pH measurement. During this period, mares had free access to Bermuda grass hay and water and were fed a commercial concentrate twice (T4 and T16). In a second group (control), four non-anesthetized mares were submitted to 8 h of fasting followed by nasogastric intubation. Gastric juice samples were then collected at T0, T15, T30, T45, T60, T75, and T90. During this period, mares did not receive food or water. After 45 min, mares had free access to Bermuda grass hay and water, and gastric juice samples were collected every hour for four hours (T1 to T4). In a third group comprising ten non-fasted, non-anesthetized mares with free access to Bermuda grass hay and water, gastric juice samples were collected 30 min after concentrate intake (T0). In anesthetized mares, blood gastrin levels were measured prior to anesthesia (8 h fasting; baseline), during recovery from anesthesia, and 4 months after the anesthetic procedure, 90 min after the morning meal. Mean values of gastric juice pH remained acidic during general anesthesia. Mean pH values were within the physiological range (4.52 ± 1.69) and did not differ significantly between time points (T15-T90; p > 0.05). After recovery from anesthesia, mean gastric pH values increased and remained in the alkaline range throughout the 24 h period of evaluation. Significant differences were observed between T0 (4.88 ± 2.38), T5 (7.08 ± 0.89), T8 (7.43 ± 0.22), T9 (7.28 ± 0.36), T11 (7.26 ± 0.71), T13 (6.74 ± 0.90), and T17 (6.94 ± 1.04) (p < 0.05). The mean gastric juice pH ranged from weakly acidic to neutral or weakly alkaline in all groups, regardless of food and water intake (i.e., in the fasted, non-fasted, and fed states). Mean gastric pH measured in the control group did not differ from values measured during the 24 h post-anesthesia period or in the non-fasted group. Gastrin concentrations increased significantly during the post-anesthetic period compared to baseline (20.15 ± 7.65 pg/mL and 15.15 ± 3.82 pg/mL respectively; p < 0.05). General inhalation anesthesia and dorsal recumbency did not affect gastric juice pH, which remained acidic and within the physiological range. Gastric juice pH was weakly alkaline after recovery from anesthesia and in the fasted and fed states. Serum gastrin levels increased in response to general inhalation anesthesia in dorsal recumbency and were not influenced by fasting. Preventive pharmacological measures are not required in horses submitted to general anesthesia and dorsal recumbency.

Gastrin Releasing Peptide Receptors-targeted PET Diagnostics and Radionuclide Therapy for Prostate Cancer Management: Preclinical and Clinical Developments of the Past 5 Years.

Each tumor has its own distinctive molecular identity. Treatment, therefore, should be tailored to this unique cancer phenotype. Theragnostics uses the same compound for targeted imaging and treatment, radiolabeled to an appropriate radionuclide, respectively. Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate cancer, and radiolabeled GRPR antagonists have shown high diagnostic performance at staging and biochemical recurrence. Several GRPR-targeting theragnostic compounds have been developed preclinically. Their translation into clinics is underway with 4 clinical trials recruiting participants with GRPR-expressing tumors.

Proton Pump Inhibitor Associated Multiple Gastric Hyperplastic Polyps With Uncontrollable Bleeding: A Case Report.

BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.

Gastrin-releasing peptide receptor (GRPR) as a novel biomarker and therapeutic target in prostate cancer.

Aim: This comprehensive review aims to explore the potential applications of Gastrin-releasing peptide receptor (GRPR) in the diagnosis and treatment of prostate cancer. Additionally, the study investigates the role of GRPR in prognostic assessment for individuals afflicted with prostate cancer.Methods: The review encompasses a thorough examination of existing literature and research studies related to the upregulation of GRPR in various tumor types, with a specific focus on prostate. The review also evaluates the utility of GRPR as a molecular target in prostate cancer research, comparing its significance to the well-established Prostate-specific membrane antigen (PSMA). The integration of radionuclide-targeted therapy with GRPR antagonists is explored as an innovative therapeutic approach for individuals with prostate cancer.Results: Research findings suggest that GRPR serves as a promising molecular target for visualizing low-grade prostate cancer. Furthermore, it is demonstrated to complement the detection of lesions that may be negative for PSMA. The integration of radionuclide-targeted therapy with GRPR antagonists presents a novel therapeutic paradigm, offering potential benefits for individuals undergoing treatment for prostate cancer.Conclusions: In conclusion, this review highlights the emerging role of GRPR in prostate cancer diagnosis and treatment. Moreover, the integration of radionuclide-targeted therapy with GRPR antagonists introduces an innovative therapeutic approach that holds promise for improving outcomes in individuals dealing with prostate cancer. The potential prognostic value of GRPR in assessing the disease's progression adds another dimension to its clinical significance in the realm of urology.

Pepsinogen II and a no-pickled food diet are risk factors for female patients with anxiety: a cross-sectional study.

OBJECTIVES: No studies have evaluated the relationship between lifestyle and Pepsinogen (PG)I, PGII and Gastrin (G)17 in patients with anxiety. Using data from the Affiliated Hospital of Xuzhou Medical University study, we aimed to identify factors associated with anxiety. METHODS: We conducted a retrospective cross-sectional observational study involving 779 Chinese healthy checkup participants (301 males; mean age, 47.60±16.17 years) who underwent stomach-related health examinations. RESULTS: Anxiety was defined as a Hamilton Anxiety Scale (HAM-A) Scale score ≥14. The odds ratios, with 95% confidence intervals, were calculated using binary logistic analysis to assess the risk of anxiety and healthy checkup participants while adjusting for several covariates. In the HAM-A≥14 group (anxiety group), sex, PGII and pickled dishes were independent influencing factors. Binary logistic regression analysis revealed a significant difference in anxiety risk between the high PGII group and the low PGII group for females (P=0.005). There was also a significant difference in anxiety risk between the groups consuming pickled and non-pickled food for females (P=0.010). Logistic regression analysis indicated a higher risk of anxiety in females aged ≤50 years who belonged to the high PGII + no pickled foods group. CONCLUSIONS: Our study revealed that in females aged ≤50 years, high levels of PGII and no pickled foods were associated with a higher risk of anxiety.

Distribution of cionin, a cholecystokinin/gastrin family peptide, and its receptor in the central nervous system of Ciona intestinalis type A.

The cholecystokinin (CCK)/gastrin family peptides are involved in regulation of feeding and digestion in vertebrates. In the ascidian Ciona intestinalis type A (Ciona robusta), cionin, a CCK/gastrin family peptide, has been identified. Cionin is expressed exclusively in the central nervous system (CNS). In contrast, cionin receptor expression has been detected in the CNS, digestive tract, and ovary. Although cionin has been reported to be involved in ovulation, its physiological function in the CNS remains to be investigated. To elucidate its neural function, in the present study, we analyzed the expression of cionin and cionin receptors in the CNS. Cionin was expressed mainly in neurons residing in the anterior region of the cerebral ganglion. In contrast, the gene expressin of the cionin receptor gene CioR1, was detected in the middle part of the cerebral ganglion and showed a similar expression pattern to that of VACHT, a cholinergic neuron marker gene. Moreover, CioR1 was found to be expressed in cholinergic neurons. Consequently, these results suggest that cionin interacts with cholinergic neurons as a neurotransmitter or neuromodulator via CioR1. This study provides insights into a biological role of a CCK/gastrin family peptide in the CNS of ascidians.

Severe Anemia from Multiple Gastric Hyperplastic Polyps in a Hemodialysis Patient after Long-term Use of a Proton-pump Inhibitor.

A 90-year-old man on maintenance hemodialysis was admitted due to severe symptomatic anemia. Biopsies under esophagogastroduodenoscopy demonstrated that the cause of anemia was intermittent blood oozing from multiple gastric hyperplastic polyps. Even after successful eradication of Helicobacter pylori, he showed hypergastrinemia (480 pg/mL) owing to esomeprazole (proton-pump inhibitor) therapy for the past 4.5 years to treat reflux esophagitis. Seven months after we switched esomeprazole to famotidine (H2-receptor antagonist), those gastric polyps and anemia were remarkably ameliorated with lowered gastrin levels. This case indicates that long-term use of a proton-pump inhibitor triggers chronic hypergastrinemia, leading to gastric hyperplastic polyps and subsequent severe anemia.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Unnatural amino acid substitutions to improve in vivo stability and tumor uptake of 68Ga-labeled GRPR-targeted TacBOMB2 derivatives for cancer imaging with positron emission tomography.

BACKGROUND: Overexpressed in various solid tumors, gastrin-releasing peptide receptor (GRPR) is a promising cancer imaging marker and therapeutic target. Although antagonists are preferable for the development of GRPR-targeted radiopharmaceuticals due to potentially fewer side effects, internalization of agonists may lead to longer tumor retention and better treatment efficacy. In this study, we systematically investigated unnatural amino acid substitutions to improve in vivo stability and tumor uptake of a previously reported GRPR-targeted agonist tracer, [68Ga]Ga-TacBOMB2 (68Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-Thz14-NH2). RESULTS: Unnatural amino acid substitutions were conducted for Gln7, Trp8, Ala9, Val10, Gly11 and His12, either alone or in combination. Out of 25 unnatural amino acid substitutions, tert-Leu10 (Tle10) and NMe-His12 substitutions were identified to be preferable modifications especially in combination. Compared with the previously reported [68Ga]Ga-TacBOMB2, the Tle10 and NMe-His12 derived [68Ga]Ga-LW01110 showed retained agonist characteristics and improved GRPR binding affinity (Ki = 7.62 vs 1.39 nM), in vivo stability (12.7 vs 89.0% intact tracer in mouse plasma at 15 min post-injection) and tumor uptake (5.95 vs 16.6 %ID/g at 1 h post-injection). CONCLUSIONS: Unnatural amino acid substitution is an effective strategy to improve in vivo stability and tumor uptake of peptide-based radiopharmaceuticals. With excellent tumor uptake and tumor-to-background contrast, [68Ga]Ga-LW01110 is promising for detecting GRPR-expressing cancer lesions with PET. Since agonists can lead to internalization upon binding to receptors and foreseeable long tumor retention, our optimized GRPR-targeted sequence, [Tle10,NMe-His12,Thz14]Bombesin(7-14), is a promising template for use for the design of GRPR-targeted radiotherapeutic agents.

Marginal Ulcer Incidence and the Population of Gastrin Producing G cells Retained in the Gastric Pouch after Roux-en-Y Gastric Bypass: Is There a Relationship?

INTRODUCTION: Marginal ulcers are the most prevalent endoscopic abnormality after RYGB. The etiology is still poorly understood; however, an increase in acid secretion has been strongly implicated as a causal agent. Although gastrin is the greatest stimulant of acid secretion, to date, the presence of gastrin producing G cells retained in the gastric pouch, related to the occurrence of marginal ulcers, has not been evaluated. OBJECTIVE: Evaluate the density of G cells and parietal cells in the gastric pouch of RYGB patients with a diagnosis of marginal ulcer on the post-op EGD. METHOD: We retrospectively evaluated 1104 gastric bypasses performed between 2010 and 2020. Patients with marginal ulcer who met the inclusion criteria and controls were selected from this same population. Endoscopic gastric pouch biopsies were evaluated using immunohistochemical study and HE staining to assess G cell and parietal cell density. RESULTS: In total, 572 (51.8%) of the patients performed endoscopic follow-up after RYGB. The incidence of marginal ulcer was 23/572 (4%), and 3 patients required revision surgery due to a recalcitrant ulcer. The mean time for ulcer identification was 24.3 months (2-62). G cell count per high-power field (× 400) was statistically higher in the ulcer group (p < 0.05). There was no statistical difference in parietal cell density between groups (p 0.251). CONCLUSION: Patients with a marginal ulcer after gastric bypass present a higher density of gastrin-producing G cells retained in the gastric pouch.

The role of gastrin 17 and pepsinogen I:pepsinogen II ratio in pathological diagnosis and endoscopic selection in gastritis patients.

BACKGROUND: The noninvasive serum markers pepsinogen I (PGI), pepsinogen II (PGII), gastrin-17 (G17), and PGI:PGII ratio (PGR) have recently been proposed as a new tool for predicting various gastric pathologies. METHODS: A total of 83 gastritis patients confirmed by gastroscopy were enrolled, with 78 undergoing concurrent colonoscopies. The control group included 99 healthy subjects. Enzyme-linked immunosorbent assay was used to detect PGI, PGII, G17, and PGR. The performance of serological analysis for detecting gastritis pathology was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The G17 and PGII levels increased significantly (P < .001), whereas PGR levels decreased (P = .001) in the gastritis group. The ROC analysis revealed that PGR had a sensitivity and specificity of 70.83% and 86.67%, respectively, in predicting Helicobacter pylori-infected gastritis and a sensitivity and specificity of 88% and 65.52%, respectively, in predicting active gastritis. The G17 levels were significantly elevated in gastritis patients undergoing concurrent colonoscopies (P < .05). CONCLUSION: Pepsinogen I:pepsinogen II ratio was found to be a useful predictor of active gastritis and H pylori-infected gastritis. Furthermore, G17 was found to be closely related to pathological conditions found by colonoscopy and may provide recommendations for whether gastritis patients should undergo a concurrent colonoscopy.

Neglected function of gastrin to reduce feeding in Siberian sturgeon (Acipenser baerii) via cholecystokinin receptor B.

Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.